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James G Fox - One of the best experts on this subject based on the ideXlab platform.

  • Comparative chemical and biological characterization of the lipopolysaccharides of gastric and enterohepatic Helicobacters.
    Helicobacter, 2004
    Co-Authors: Sean O. Hynes, Lennart Larsson, Elisa Yaquian, Åsa Ljungh, James G Fox, John A. Ferris, Bogumiła Szponar, Torkel Wadström, Jani O'rourke, Marguerite Clyne
    Abstract:

    Background. The lipopolysaccharide of Helicobacter pylori plays an important role in colonization and pathogenicity. The present study sought to compare structural and biological features of lipopolysaccharides from gastric and enterohepatic Helicobacter spp. not previously characterized. Materials and methods. Purified lipopolysaccharides from four gastric Helicobacter spp. (H. pylori, Helicobacter felis, Helicobacter bizzozeronii and Helicobacter Mustelae) and four enterohepatic Helicobacter spp. (Helicobacter hepaticus, Helicobacter bilis, ‘Helicobacter sp. flexispira’ and Helicobacter pullorum) were structurally characterized using electrophoretic, serological and chemical methods. Results. Structural insights into all three moieties of the lipopolysaccharides, i.e. lipid A, core and Opolysaccharide chains, were gained. All species expressed lipopolysaccharides bearing an O-polysaccharide chain, but H. Mustelae and H. hepaticus produced truncated semirough lipopolysaccharides. However, in contrast to lipopolysaccharides of H. pylori and H. Mustelae, no blood group mimicry was detected in the other Helicobacter spp. examined. Intraspecies, but not interspecies, fatty acid profiles of lipopolysaccharides were identical within the genus. Although shared lipopolysaccharide-core epitopes with H. pylori occurred, differing structural characteristics were noted in this lipopolysaccharide region of some Helicobacter spp. The lipopolysaccharides of the gastric Helicobacters, H. bizzozeronii and H. Mustelae, had relative Limulus amoebocyte lysate activities which clustered around that of H. pylori lipopolysaccharide, whereas H. bilis, ‘Helicobacter sp. flexispira’ and H. hepaticus formed a cluster with approximately 1000‐10,000-fold lower activities. H. pullorum lipopolysaccharide had the highest relative Limulus amoebocyte lysate activity of all the Helicobacter lipopolysaccharides (10-fold higher than that of H. pylori lipopolysaccharide), and all the lipopolysaccharides of enterohepatic Helicobacter spp. were capable of inducing nuclear factor-Kappa B(NF-κB) activation. Conclusions. The collective results demonstrate the structural heterogeneity and pathogenic potential of lipopolysaccharides of the Helicobacter genus as a group and these differences in lipopolysaccharides may be indicative of adaptation of the bacteria to different ecological niches.

  • novel intestinal Helicobacter species isolated from cotton top tamarins saguinus oedipus with chronic colitis
    Journal of Clinical Microbiology, 1999
    Co-Authors: Kim E Saunders, Bruce J. Paster, Floyd E. Dewhirst, Zeli Shen, Charles A Dangler, James G Fox
    Abstract:

    A disease similar to ulcerative colitis in humans has been identified in cotton-top tamarins (CTTs) in captivity. The clinical signs include weight loss, diarrhea, and rectal bleeding with the pathological features and biochemical abnormalities of ulcerative colitis. Approximately 25 to 40% of these animals develop colon cancer after 2 to 5 years of captivity. An infectious etiology has been proposed; however, no microbial agent to date has been identified. Helicobacter spp. have been associated with enterocolitis and inflammatory bowel disease (IBD) in humans and animals. Infection with Helicobacter pylori or Helicobacter Mustelae is associated with an increased risk of gastric adenocarcinoma and lymphoma of the mucosa-associated lymphoid tissue. Helicobacter hepaticus causes hepatitis, hepatic adenomas, and hepatocellular carcinomas in susceptible strains of mice. The aim of this study was to assess a colony of CTTs with a high incidence of IBD and colon cancer for the presence of colonic Helicobacter spp. A fusiform, gram-negative bacterium with bipolar flagella and periplasmic fibers was isolated from the feces of CTTs. The bacterium grew under microaerobic conditions at 37 and 42°C but not at 25°C, did not hydrolyze urea, was positive for catalase and oxidase, did not reduce nitrate to nitrite, did not hydrolyze indoxyl acetate or alkaline phosphatase, and was resistant to nalidixic acid, cephalothin, and trimethoprim-sulfamethoxazole. On the basis of 16S rRNA gene sequence analysis, the organism was classified as a novel Helicobacter species. This is the first Helicobacter isolated from CTTs. Further studies are needed to elucidate the role of this novel Helicobacter sp. in the pathogenesis of ulcerative colitis and colonic adenocarcinoma in CTTs.

  • Use of pulsed-field gel electrophoresis to determine genomic diversity in strains of Helicobacter hepaticus from geographically distant locations.
    Journal of clinical microbiology, 1997
    Co-Authors: Kim E Saunders, Karen J. Mcgovern, James G Fox
    Abstract:

    In 1992 a helical microorganism associated with chronic active hepatitis and a high incidence of hepatocellular tumors was identified in the hepatic parenchyma of A/JCr mice. By using biochemical tests, phenotypic characterization, and 16S rRNA gene sequence analysis, the organism was classified as a novel Helicobacter species and named Helicobacter hepaticus. Recent surveys completed in our laboratory indicate that H. hepaticus is widespread in academic and commercial mouse colonies. The aim of this study was to examine the H. hepaticus genome by pulsed-field gel electrophoresis (PFGE) to determine the degree of genomic variation and genomic size. This technique has been used to identify significant genomic diversity among strains of Helicobacter pylori and to demonstrate only slight genomic diversity among strains of Helicobacter Mustelae. Genomic DNAs from 11 isolates of H. hepaticus from the United States, Germany, France, and The Netherlands were subjected to PFGE after digestion with SmaI. Isolates from three independent sources within the United States had very similar PFGE patterns, suggesting that the genomic DNAs of these isolates are conserved. Genomic DNA isolated from a fourth source within the United States had a PFGE pattern different from those of the other U.S. isolates. Isolates obtained from Germany, France, and The Netherlands had PFGE patterns that differed markedly from those of the U.S. isolates and from one another. The use of DNA fingerprinting may be useful in subsequent epidemiological studies of H. hepaticus when the source and method of spread of this murine pathogen need to be ascertained. By PFGE, the genomic size of H. hepaticus is estimated to be roughly 1.3 Mb, which compares to 1.67 Mb for H. pylori and 1.7 Mb for H. Mustelae.

  • Helicobacter Mustelae associated hypergastrinemia in ferrets mustela putorius furo
    American Journal of Veterinary Research, 1996
    Co-Authors: S E Perkins, James G Fox, J H Walsh
    Abstract:

    OBJECTIVE: To determine whether ferrets naturally infected with Helicobacter Mustelae were hypergastrinemic, compared with ferrets that were specific-pathogen-free (SPF) for H Mustelae. DESIGN: Plasma gastrin concentrations in H Mustelae-infected and SPF ferrets were measured at 3 time points and compared to determine whether H Mustelae was associated with hypergastrinemia. ANIMALS: 21 H Mustelae-infected ferrets and 10 SPF ferrets. PROCEDURE: The H Mustelae status of the ferrets was confirmed prior to commencement of the study. Gastric endoscopy was used to obtain gastric mucosal pinch biopsy specimens that were processed for rapid-urease assay, microaerophilic culturing, and histologic evaluation. Plasma gastrin concentrations were determined at 3 time points: baseline after a 12-hour nonfeeding period, and 30 and 60 minutes after oral administration of a standardized meal. Gastrin was measured by radioimmunoassay. RESULTS: The results for the H Mustelae-infected group (mean +/- SEM pg/ml) were: baseline, 54.4 +/- 2.56; 30 minutes, 94.5 +/- 6.05; and 60 minutes, 82.6 +/- 5.73. The SPF group results were: baseline, 55.8 +/- 7.35; 30 minutes, 80.8 +/- 5.77; and 60 minutes, 59.7 +/- 4.95. There was a significant (P < 0.01) difference at the 60-minute time point between the 2 groups of animals. The H Mustelae group had a 17% higher mean gastrin value at 30 minutes. CONCLUSIONS: Helicobacter Mustelae is associated with hypergastrinemia in ferrets. CLINICAL RELEVANCE: Helicobacter-induced hypergastrinemia may be related to the pathogenesis of peptic ulcer disease in ferrets.

  • Gastric disease in ferrets: effects of Helicobacter Mustelae, nitrosamines and reconstructive gastric surgery.
    European journal of gastroenterology & hepatology, 1994
    Co-Authors: James G Fox
    Abstract:

    PURPOSE Animal models are being used to study the mechanisms by which Helicobacter spp. induce gastric disease. To assess the effects of a natural gastric pathogen, Helicobacter Mustelae, in the development of chronic gastritis, premalignancy and cancer, the ferret model was studied under natural and experimental conditions. ANIMALS AND METHODS H. Mustelae-infected ferrets were used to study the metabolism of nitrates/nitrites, which are dietary and endogenously formed substances that have been linked to gastric cancer. The ferret was also manipulated by performing gastric reconstructive surgery to study the processing of nitrite and nitrate and to assess the effect of surgery on gastric pathology. In addition, the ferret was tested for its suitability as an animal model for the induction of gastric cancer by oral dosing with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The influence of these variables on gastric pathology and/or metabolic outcomes was examined, and the results in ferrets were compared to findings in humans. RESULTS AND CONCLUSIONS The ferret appears to be an ideal model for studying various gastric parameters and how these factors influence the development of H. Mustelae-associated gastric disease. Gastric reconstructive surgery did not effect nitrite processing or overall severity of gastritis in ferrets. However, a single dose of MNNG (50 mg/kg) produced an unprecedented 90% gastric carcinoma in H. Mustelae-infected ferrets. This implies that chronic inflammation induced by the bacterium is a cofactor in gastric carcinogenesis.

Arnoud H. M. Van Vliet - One of the best experts on this subject based on the ideXlab platform.

  • DOI 10.1007/s10534-006-9028-9 Metal-responsive gene regulation and metal transport in Helicobacter species
    2013
    Co-Authors: Arnoud H. M. Van Vliet
    Abstract:

    Abstract Helicobacter species are among the most successful colonizers of the mammalian gastrointestinal and hepatobiliary tract. Colonization is usually lifelong, indicating that Helicobacter species have evolved intricate mechanisms of dealing with stresses encountered during colonization of host tissues, like restriction of essential metal ions. The recent availability of genome sequences of the human gastric pathogen Helicobacter pylori, the murine enterohepatic pathogen Helicobacter hepaticus and the unannotated genome sequence of the ferret gastric pathogen Helicobacter Mustelae has allowed for comparitive genome analyses. In this review we present such analyses for metal transporters, metal-storage and metal-responsive regulators in these three Helicobacter species, and discuss possible contributions of the differences in metal metabolism in adaptation to the gastric or enterohepatic niches occupied by Helicobacter species

  • An ABC transporter and a TonB ortholog contribute to Helicobacter Mustelae nickel and cobalt acquisition
    Infection and immunity, 2010
    Co-Authors: Jeroen Stoof, Ernst J. Kuipers, Gerard Klaver, Arnoud H. M. Van Vliet
    Abstract:

    The genomes of Helicobacter species colonizing the mammalian gastric mucosa (like Helicobacter pylori) contain a large number of genes annotated as iron acquisition genes but only few nickel acquisition genes, which contrasts with the central position of nickel in the urease-mediated acid resistance of these gastric pathogens. In this study we have investigated the predicted iron and nickel acquisition systems of the ferret pathogen Helicobacter Mustelae. The expression of the outer membrane protein-encoding frpB2 gene was iron and Fur repressed, whereas the expression of the ABC transporter genes fecD and ceuE was iron and Fur independent. The inactivation of the two tonB genes showed that TonB1 is required for heme utilization, whereas the absence of TonB2 only marginally affected iron-dependent growth but led to reduced cellular nickel content and urease activity. The inactivation of the fecD and ceuE ABC transporter genes did not affect iron levels but resulted in significantly reduced urease activity and cellular nickel content. Surprisingly, the inactivation of the nixA nickel transporter gene affected cellular nickel content and urease activity only when combined with the inactivation of other nickel acquisition genes, like fecD or ceuE. The FecDE ABC transporter is not specific for nickel, since an fecD mutant also showed reduced cellular cobalt levels and increased cobalt resistance. We conclude that the H. Mustelae fecDE and ceuE genes encode an ABC transporter involved in nickel and cobalt acquisition, which works independently of the nickel transporter NixA, while TonB2 is required primarily for nickel acquisition, with TonB1 being required for heme utilization.

  • Characterization of NikR-responsive promoters of urease and metal transport genes of Helicobacter Mustelae
    2010
    Co-Authors: Jeroen Stoof, Ernst J. Kuipers, Arnoud H. M. Van Vliet
    Abstract:

    Abstract The NikR protein is a nickel-responsive regulator, which in the gastric pathogen Helicobacter pylori controls expression of nickel-transporters and the nickel-cofactored urease acid resistance determi-nant. Although NikR-DNA interaction has been well studied, the Helicobacter NikR operator site remains poorly defined. In this study we have identified the NikR operators in the promoters of two inversely nickel-regulated urease operons (ureAB and ureA2B2) in the ferret pathogen Helicobacter Mustelae, and have used bioinformatic approaches for the prediction of putative NikR operators in the genomes of four urease-positive Helicobacter species. Helicobacter Mustelae NikR bound to the ureA2 promoter to a sequence overlapping with the-35 promoter region, leading t

  • An ABC transporter and a TonB ortholog contribute to Helicobacter Mustelae nickel and cobalt acquisition. Infect. Immun
    2010
    Co-Authors: Jeroen Stoof, Ernst J. Kuipers, Gerard Klaver, Arnoud H. M. Van Vliet
    Abstract:

    The genomes of Helicobacter species colonizing the mammalian gastric mucosa (like Helicobacter pylori) contain a large number of genes annotated as iron acquisition genes but only few nickel acquisition genes, which contrasts with the central position of nickel in the urease-mediated acid resistance of these gastric pathogens. In this study we have investigated the predicted iron and nickel acquisition systems of the ferret pathogen Helicobacter Mustelae. The expression of the outer membrane protein-encoding frpB2 gene was iron and Fur repressed, whereas the expression of the ABC transporter genes fecD and ceuE was iron and Fur independent. The inactivation of the two tonB genes showed that TonB1 is required for heme utilization, whereas the absence of TonB2 only marginally affected iron-dependent growth but led to reduced cellular nickel content and urease activity. The inactivation of the fecD and ceuE ABC transporter genes did not affect iron levels but resulted in significantly reduced urease activity and cellular nickel content. Surprisingly, the inactivation of the nixA nickel transporter gene affected cellular nickel content and urease activity only when combined with the inactivation of other nickel acquisition genes, like fecD or ceuE. The FecDE ABC transporter is not specific for nickel, since an fecD mutant also showed reduced cellular cobalt levels and increased cobalt resistance. We conclude that the H. Mustelae fecDE and ceuE genes encode an ABC transporter involved i

  • Inverse nickel-responsive regulation of two urease enzymes in the gastric pathogen Helicobacter Mustelae
    Environmental microbiology, 2008
    Co-Authors: Jeroen Stoof, Ernst J. Kuipers, Johannes G. Kusters, Simone Breijer, Raymond G.j. Pot, Daan Van Der Neut, Arnoud H. M. Van Vliet
    Abstract:

    The acidic gastric environment of mammals can be chronically colonized by pathogenic Helicobacter species, which use the nickel-dependent urea-degrading enzyme urease to confer acid resistance. Nickel availability in the mammal host is low, being mostly restricted to vegetarian dietary sources, and thus Helicobacter species colonizing carnivores may be subjected to episodes of nickel deficiency and associated acid sensitivity. The aim of this study was to investigate how these Helicobacter species have adapted to the nickel-restricted diet of their carnivorous host. Three carnivore-colonizing Helicobacter species express a second functional urea-degrading urease enzyme (UreA2B2), which functions as adaptation to nickel deficiency. UreA2B2 was not detected in seven other Helicobacter species, and is in Helicobacter Mustelae only expressed in nickel-restricted conditions, and its expression was higher in iron-rich conditions. In contrast to the standard urease UreAB, UreA2B2 does not require activation by urease or hydrogenase accessory proteins, which mediate nickel incorporation into these enzymes. Activity of either UreAB or UreA2B2 urease allowed survival of a severe acid shock in the presence of urea, demonstrating a functional role for UreA2B2 in acid resistance. Pathogens often express colonization factors which are adapted to their host. The UreA2B2 urease could represent an example of pathogen adaptation to the specifics of the diet of their carnivorous host, rather than to the host itself.

Jeroen Stoof - One of the best experts on this subject based on the ideXlab platform.

  • An ABC transporter and a TonB ortholog contribute to Helicobacter Mustelae nickel and cobalt acquisition
    Infection and immunity, 2010
    Co-Authors: Jeroen Stoof, Ernst J. Kuipers, Gerard Klaver, Arnoud H. M. Van Vliet
    Abstract:

    The genomes of Helicobacter species colonizing the mammalian gastric mucosa (like Helicobacter pylori) contain a large number of genes annotated as iron acquisition genes but only few nickel acquisition genes, which contrasts with the central position of nickel in the urease-mediated acid resistance of these gastric pathogens. In this study we have investigated the predicted iron and nickel acquisition systems of the ferret pathogen Helicobacter Mustelae. The expression of the outer membrane protein-encoding frpB2 gene was iron and Fur repressed, whereas the expression of the ABC transporter genes fecD and ceuE was iron and Fur independent. The inactivation of the two tonB genes showed that TonB1 is required for heme utilization, whereas the absence of TonB2 only marginally affected iron-dependent growth but led to reduced cellular nickel content and urease activity. The inactivation of the fecD and ceuE ABC transporter genes did not affect iron levels but resulted in significantly reduced urease activity and cellular nickel content. Surprisingly, the inactivation of the nixA nickel transporter gene affected cellular nickel content and urease activity only when combined with the inactivation of other nickel acquisition genes, like fecD or ceuE. The FecDE ABC transporter is not specific for nickel, since an fecD mutant also showed reduced cellular cobalt levels and increased cobalt resistance. We conclude that the H. Mustelae fecDE and ceuE genes encode an ABC transporter involved in nickel and cobalt acquisition, which works independently of the nickel transporter NixA, while TonB2 is required primarily for nickel acquisition, with TonB1 being required for heme utilization.

  • Characterization of NikR-responsive promoters of urease and metal transport genes of Helicobacter Mustelae
    2010
    Co-Authors: Jeroen Stoof, Ernst J. Kuipers, Arnoud H. M. Van Vliet
    Abstract:

    Abstract The NikR protein is a nickel-responsive regulator, which in the gastric pathogen Helicobacter pylori controls expression of nickel-transporters and the nickel-cofactored urease acid resistance determi-nant. Although NikR-DNA interaction has been well studied, the Helicobacter NikR operator site remains poorly defined. In this study we have identified the NikR operators in the promoters of two inversely nickel-regulated urease operons (ureAB and ureA2B2) in the ferret pathogen Helicobacter Mustelae, and have used bioinformatic approaches for the prediction of putative NikR operators in the genomes of four urease-positive Helicobacter species. Helicobacter Mustelae NikR bound to the ureA2 promoter to a sequence overlapping with the-35 promoter region, leading t

  • An ABC transporter and a TonB ortholog contribute to Helicobacter Mustelae nickel and cobalt acquisition. Infect. Immun
    2010
    Co-Authors: Jeroen Stoof, Ernst J. Kuipers, Gerard Klaver, Arnoud H. M. Van Vliet
    Abstract:

    The genomes of Helicobacter species colonizing the mammalian gastric mucosa (like Helicobacter pylori) contain a large number of genes annotated as iron acquisition genes but only few nickel acquisition genes, which contrasts with the central position of nickel in the urease-mediated acid resistance of these gastric pathogens. In this study we have investigated the predicted iron and nickel acquisition systems of the ferret pathogen Helicobacter Mustelae. The expression of the outer membrane protein-encoding frpB2 gene was iron and Fur repressed, whereas the expression of the ABC transporter genes fecD and ceuE was iron and Fur independent. The inactivation of the two tonB genes showed that TonB1 is required for heme utilization, whereas the absence of TonB2 only marginally affected iron-dependent growth but led to reduced cellular nickel content and urease activity. The inactivation of the fecD and ceuE ABC transporter genes did not affect iron levels but resulted in significantly reduced urease activity and cellular nickel content. Surprisingly, the inactivation of the nixA nickel transporter gene affected cellular nickel content and urease activity only when combined with the inactivation of other nickel acquisition genes, like fecD or ceuE. The FecDE ABC transporter is not specific for nickel, since an fecD mutant also showed reduced cellular cobalt levels and increased cobalt resistance. We conclude that the H. Mustelae fecDE and ceuE genes encode an ABC transporter involved i

  • Characterization of NikR-responsive promoters of urease and metal transport genes of Helicobacter Mustelae
    BioMetals, 2009
    Co-Authors: Jeroen Stoof, Ernst J. Kuipers, Arnoud H. M. Vliet
    Abstract:

    The NikR protein is a nickel-responsive regulator, which in the gastric pathogen Helicobacter pylori controls expression of nickel-transporters and the nickel-cofactored urease acid resistance determinant. Although NikR-DNA interaction has been well studied, the Helicobacter NikR operator site remains poorly defined. In this study we have identified the NikR operators in the promoters of two inversely nickel-regulated urease operons ( ureAB and ureA2B2 ) in the ferret pathogen Helicobacter Mustelae , and have used bioinformatic approaches for the prediction of putative NikR operators in the genomes of four urease-positive Helicobacter species. Helicobacter Mustelae NikR bound to the ureA2 promoter to a sequence overlapping with the −35 promoter region, leading to repression. In contrast, NikR binding to a site far upstream of the canonical σ^80 promoter in the H. Mustelae ureA promoter resulted in transcriptional induction, similar to the situation in H. pylori . Using H. pylori NikR operators and the newly identified H. Mustelae NikR operators a new consensus sequence was generated (TRWYA-N_15-TRWYA), which was used to screen the genomes of four urease-positive Helicobacter species ( H. Mustelae , H. pylori , H. acinonychis and H. hepaticus ) for putative NikR-regulated promoters. One of these novel putative NikR-regulated promoters in H. Mustelae is located upstream of a putative TonB-dependent outer membrane protein designated NikH, which displayed nickel-responsive expression. Insertional inactivation of the nikH gene in H. Mustelae resulted in a significant decrease in urease activity, and this phenotype was complemented by nickel-supplementation of the growth medium, suggesting a function for NikH in nickel transport accross the outer membrane. In conclusion, the H. Mustelae NikR regulator directly controls nickel-responsive regulation of ureases and metal transporters . The improved consensus NikR operator sequence allows the prediction of additional NikR targets in Helicobacter genomes, as demonstrated by the identification of a new nickel-repressed outer membrane protein in H. Mustelae .

  • Inverse nickel-responsive regulation of two urease enzymes in the gastric pathogen Helicobacter Mustelae
    Environmental microbiology, 2008
    Co-Authors: Jeroen Stoof, Ernst J. Kuipers, Johannes G. Kusters, Simone Breijer, Raymond G.j. Pot, Daan Van Der Neut, Arnoud H. M. Van Vliet
    Abstract:

    The acidic gastric environment of mammals can be chronically colonized by pathogenic Helicobacter species, which use the nickel-dependent urea-degrading enzyme urease to confer acid resistance. Nickel availability in the mammal host is low, being mostly restricted to vegetarian dietary sources, and thus Helicobacter species colonizing carnivores may be subjected to episodes of nickel deficiency and associated acid sensitivity. The aim of this study was to investigate how these Helicobacter species have adapted to the nickel-restricted diet of their carnivorous host. Three carnivore-colonizing Helicobacter species express a second functional urea-degrading urease enzyme (UreA2B2), which functions as adaptation to nickel deficiency. UreA2B2 was not detected in seven other Helicobacter species, and is in Helicobacter Mustelae only expressed in nickel-restricted conditions, and its expression was higher in iron-rich conditions. In contrast to the standard urease UreAB, UreA2B2 does not require activation by urease or hydrogenase accessory proteins, which mediate nickel incorporation into these enzymes. Activity of either UreAB or UreA2B2 urease allowed survival of a severe acid shock in the presence of urea, demonstrating a functional role for UreA2B2 in acid resistance. Pathogens often express colonization factors which are adapted to their host. The UreA2B2 urease could represent an example of pathogen adaptation to the specifics of the diet of their carnivorous host, rather than to the host itself.

Christine Josenhans - One of the best experts on this subject based on the ideXlab platform.

  • Comparative genomics and proteomics of Helicobacter Mustelae, an ulcerogenic and carcinogenic gastric pathogen
    BMC Genomics, 2010
    Co-Authors: Paul W. O'toole, William J Snelling, Brian M Forde, Christine Josenhans, Robert Lj Graham, Geoff Mcmullan, Carlos Canchaya, Kim R Hardie, Julian Parkhill, Eugenio Belda
    Abstract:

    Background Helicobacter Mustelae causes gastritis, ulcers and gastric cancer in ferrets and other mustelids. H. Mustelae remains the only Helicobacter other than H. pylori that causes gastric ulceration and cancer in its natural host. To improve understanding of H. Mustelae pathogenesis, and the ulcerogenic and carcinogenic potential of Helicobacters in general, we sequenced the H. Mustelae genome, and identified 425 expressed proteins in the envelope and cytosolic proteome. Results The H. Mustelae genome lacks orthologs of major H. pylori virulence factors including CagA, VacA, BabA, SabA and OipA. However, it encodes ten autotransporter surface proteins, seven of which were detected in the expressed proteome, and which, except for the Hsr protein, are of unknown function. There are 26 putative outer membrane proteins in H. Mustelae , some of which are most similar to the Hof proteins of H. pylori . Although homologs of putative virulence determinants of H. pylori (NapA, plasminogen adhesin, collagenase) and Campylobacter jejuni (CiaB, Peb4a) are present in the H. Mustelae genome, it also includes a distinct complement of virulence-related genes including a haemagglutinin/haemolysin protein, and a glycosyl transferase for producing blood group A/B on its lipopolysaccharide. The most highly expressed 264 proteins in the cytosolic proteome included many corresponding proteins from H. pylori , but the rank profile in H. Mustelae was distinctive. Of 27 genes shown to be essential for H. pylori colonization of the gerbil, all but three had orthologs in H. Mustelae , identifying a shared set of core proteins for gastric persistence. Conclusions The determination of the genome sequence and expressed proteome of the ulcerogenic species H Mustelae provides a comparative model for H. pylori to investigate bacterial gastric carcinogenesis in mammals, and to suggest ways whereby cag minus H. pylori strains might cause ulceration and cancer. The genome sequence was deposited in EMBL/GenBank/DDBJ under accession number FN555004.

  • comparative genomics and proteomics of Helicobacter Mustelae an ulcerogenic and carcinogenic gastric pathogen
    BMC Genomics, 2010
    Co-Authors: Paul W Otoole, William J Snelling, Brian M Forde, Christine Josenhans, Geoff Mcmullan, Carlos Canchaya, Kim R Hardie, Julian Parkhill, Robert Graham, Eugenio Belda
    Abstract:

    Background Helicobacter Mustelae causes gastritis, ulcers and gastric cancer in ferrets and other mustelids. H. Mustelae remains the only Helicobacter other than H. pylori that causes gastric ulceration and cancer in its natural host. To improve understanding of H. Mustelae pathogenesis, and the ulcerogenic and carcinogenic potential of Helicobacters in general, we sequenced the H. Mustelae genome, and identified 425 expressed proteins in the envelope and cytosolic proteome.

  • Adherence of isogenic flagellum-negative mutants of Helicobacter pylori and Helicobacter Mustelae to human and ferret gastric epithelial cells.
    Infection and immunity, 2000
    Co-Authors: Marguerite Clyne, Christine Josenhans, Tadhg O'croinin, Brendan Drumm
    Abstract:

    Isogenic flagellum-negative mutants of Helicobacter pylori and Helicobacter Mustelae were screened for their ability to adhere to primary human and ferret gastric epithelial cells, respectively. We also evaluated the adherence of an H. pylori strain with a mutation in the flbA gene, a homologue of the flbF/lcrD family of genes known to be involved in the regulation of H. pylori flagellar biosynthesis. H. pylori and H. Mustelae mutants deficient in production of FlaA or FlaB and mutants deficient in the production of both FlaA and FlaB showed no reduction in adherence to primary human or ferret gastric epithelial cells compared with the wild-type parental strains. However, adherence of the H. pylori flbA mutant to human gastric cells was significantly reduced compared to the adherence of the wild-type strain. These results show that flagella do not play a direct role in promoting adherence of H. pylori or H. Mustelae to gastric epithelial cells. However, genes involved in the regulation of H. pylori flagellar biosynthesis may also regulate the production of an adhesin.

  • Infection of the ferret stomach by isogenic flagellar mutant strains of Helicobacter Mustelae.
    Infection and immunity, 1997
    Co-Authors: K A Andrutis, Christine Josenhans, Robert P. Marini, L Yan, David B Schauer, Li X, Sebastian Suerbaum
    Abstract:

    Helicobacter Mustelae, like Helicobacter pylori, possesses two flagellin proteins, FlaA and FlaB. Isogenic mutant strains of H. Mustelae have been constructed by disruption of the flaA or flaB gene with a kanamycin resistance cassette or by introduction of both a kanamycin and a chloramphenicol resistance gene to produce a double mutant. To determine whether one or both flagellin proteins are necessary for colonization and persistence of infection with H. Mustelae, 19 ferrets, specific pathogen free for H. Mustelae, were given either the HMF1 flaA::km (weakly motile), ATCC 43772 flaB::km (moderately motile), or HMF1 flaA::cat flaB::km (non-motile) mutant strain, the wild-type parent strains, or sterile broth. Gastric tissue samples were obtained during sequential gastric biopsies beginning at 3 weeks postinoculation and ending at necropsy at 3 months postinoculation. H. Mustelae infection status was determined by culture, histology, and serology. The wild-type parent strains of H. Mustelae infected all ferrets at all time points. The double-mutant strain was unable to colonize; the flaA and flaB single-mutant strains were able to initially colonize at a low level and establish persistent infection with increasing numbers of organisms over time. The severity of gastritis produced by infection with these strains of H. Mustelae correlated with the number of organisms present in the gastric mucosa. Flagellar motility is an important virulence factor for colonization and pathogenesis in the H. Mustelae ferret model.

  • Construction and characterization of an isogenic urease-negative mutant of Helicobacter Mustelae
    Infection and immunity, 1995
    Co-Authors: Jay V. Solnick, Christine Josenhans, Sebastian Suerbaum, Lucy S. Tompkins, Andagnes Labigne
    Abstract:

    Helicobacter Mustelae infects the ferret stomach and provides an opportunity to study pathogenic determinants of a Helicobacter species in its natural host. We constructed an isogenic urease-negative mutant of H. Mustelae which produced no detectable urease and showed a reduced acid tolerance. This mutant provides an opportunity to further evaluate the role of urease in the pathogenesis of Helicobacter infection.

Brendan Drumm - One of the best experts on this subject based on the ideXlab platform.

  • Antigastric autoantibodies in ferrets naturally infected with Helicobacter Mustelae.
    Infection and immunity, 2001
    Co-Authors: Tadhg Ó Cróinín, Marguerite Clyne, Ben J. Appelmelk, Brendan Drumm
    Abstract:

    Infection with Helicobacter pylori has been associated with induction of autoantibodies that cross-react with the gastric mucosa. There have been discordant reports as to whether or not these autoantibodies arise due to molecular mimicry between H. pylori and host cell antigens on parietal cells. In this study, we investigated whether molecular mimicry by H. Mustelae causes autoantibodies in infected ferrets. Serum from H. Mustelae-infected ferrets reacted with parietal cells in the ferret gastric mucosa but not with duodenal or colonic mucosa. These sera did not react with the blood group A epitope on erythrocytes or H. Mustelae lipopolysaccharide, and absorption with H. Mustelae whole cells or red blood cells did not remove autoantibodies. In conclusion, ferrets naturally infected with H. Mustelae generate antibodies that react with parietal cells, but these autoantibodies are not due to molecular mimicry.

  • Adherence of isogenic flagellum-negative mutants of Helicobacter pylori and Helicobacter Mustelae to human and ferret gastric epithelial cells.
    Infection and immunity, 2000
    Co-Authors: Marguerite Clyne, Christine Josenhans, Tadhg O'croinin, Brendan Drumm
    Abstract:

    Isogenic flagellum-negative mutants of Helicobacter pylori and Helicobacter Mustelae were screened for their ability to adhere to primary human and ferret gastric epithelial cells, respectively. We also evaluated the adherence of an H. pylori strain with a mutation in the flbA gene, a homologue of the flbF/lcrD family of genes known to be involved in the regulation of H. pylori flagellar biosynthesis. H. pylori and H. Mustelae mutants deficient in production of FlaA or FlaB and mutants deficient in the production of both FlaA and FlaB showed no reduction in adherence to primary human or ferret gastric epithelial cells compared with the wild-type parental strains. However, adherence of the H. pylori flbA mutant to human gastric cells was significantly reduced compared to the adherence of the wild-type strain. These results show that flagella do not play a direct role in promoting adherence of H. pylori or H. Mustelae to gastric epithelial cells. However, genes involved in the regulation of H. pylori flagellar biosynthesis may also regulate the production of an adhesin.

  • Molecular mimicry of ferret gastric epithelial blood group antigen A by Helicobacter Mustelae
    Gastroenterology, 1998
    Co-Authors: Tadhg Ó Cróinín, Marguerite Clyne, Brendan Drumm
    Abstract:

    Abstract Background & Aims: Molecular mimicry of Lewis blood group antigens by Helicobacter pylori may be involved in immune evasion by the bacteria and in the pathogenesis of chronic atrophic gastritis. Helicobacter Mustelae infects ferrets naturally, causing gastritis, and may be involved in ulcerogenesis. The aim of this study was to determine if H. Mustelae shows a similar form of molecular mimicry. Methods: Antibodies raised against H. Mustelae were used to stain ferret gastric tissue by immunoblotting, immunohistochemistry, and flow cytometry. Epitopes recognized by cross-reactivity were characterized by proteinase K and sodium metaperiodate treatment. Results: H. Mustelae antiserum reacted with H. Mustelae and with ferret gastric tissue. Absorption of the antiserum with H. Mustelae or ferret and rabbit gastric tissue removed the cross-reactive antibodies. Antibodies reacted with a blood group antigen A–like structure on ferret gastric epithelial cells and H. Mustelae lipopolysaccharide. Conclusions: H. Mustelae expresses a blood group–like antigen as part of its lipopolysaccharide that may be used as a method of immune evasion by mimicry of gastric epithelial cells. The cross-reactivity shown by H. Mustelae –specific antibodies with gastric mucosa may suggest a role for autoantibodies in the pathogenesis of H. Mustelae –induced gastritis in ferrets. GASTROENTEROLOGY 1998;114:690-696